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Review
. 2016 Sep 16;9(9):CD009999.
doi: 10.1002/14651858.CD009999.pub2.

Pain-relieving agents for infantile colic

Elena Biagioli  1 , Valentina Tarasco, Carla Lingua, Lorenzo Moja, Francesco Savino
Affiliations
Review

Pain-relieving agents for infantile colic

Elena Biagioli et al. Cochrane Database Syst Rev. .

Abstract

Background: Infantile colic is a common disorder in the first months of life, affecting somewhere between 4% and 28% of infants worldwide, depending on geography and definitions used. Although it is self limiting and resolves by four months of age, colic is perceived by parents as a problem that requires action. Pain-relieving agents, such as drugs, sugars and herbal remedies, have been suggested as interventions to reduce crying episodes and severity of symptoms.

Objectives: To assess the effectiveness and safety of pain-relieving agents for reducing colic in infants younger than four months of age.

Search methods: We searched the following databases in March 2015 and again in May 2016: CENTRAL, Ovid MEDLINE, Embase and PsycINFO, along with 11 other databases. We also searched two trial registers, four thesis repositories and the reference lists of relevant studies to identify unpublished and ongoing studies.

Selection criteria: We included randomised controlled trials (RCTs) and quasi-RCTs evaluating the effects of pain-relieving agents given to infants with colic.

Data collection and analysis: We used the standard methodological procedures of The Cochrane Collaboration.

Main results: We included 18 RCTs involving 1014 infants. All studies were small and at high risk of bias, often presenting major shortcomings across multiple design factors (e.g. selection, performance, attrition, lack of washout period).Three studies compared simethicone with placebo, and one with Mentha piperita; four studies compared herbal agents with placebo; two compared sucrose or glucose with placebo; five compared dicyclomine with placebo; and two compared cimetropium - one against placebo and the other at two different dosages. One multiple-arm study compared sucrose and herbal tea versus no treatment. Simethicone. Comparison with placebo revealed no difference in daily hours of crying reported for simethicone at the end of treatment in one small, low-quality study involving 27 infants. A meta-analysis of data from two cross-over studies comparing simethicone with placebo showed no difference in the number of of infants who responded positively to treatment (risk ratio (RR) 0.95, 95% confidence interval (CI) 0.73 to 1.23; 110 infants, low-quality evidence).One small study (30 participants) compared simethicone with Mentha piperita and found no difference in crying duration, number of crying episodes or number of responders. Herbal agents. We found low-quality evidence suggesting that herbal agents reduce the duration of crying compared with placebo (mean difference (MD) 1.33, 95% CI 0.71 to 1.96; three studies, 279 infants), with different magnitude of benefit noted across studies (I² = 96%). We found moderate-quality evidence indicating that herbal agents increase response over placebo (RR 2.05, 95% CI 1.56 to 2.70; three studies, 277 infants). Sucrose. One very low-quality study involving 35 infants reported that sucrose reduced hours spent crying compared with placebo (MD 1.72, 95% CI 1.38 to 2.06). Dicyclomine. We could consider only one of the five studies of dicyclomine (48 infants) for the primary comparison. In this study, more of the infants given dicyclomine responded than than those given placebo (RR 2.50, 95% CI 1.17 to 5.34). Cimetropium bromide. Data from one very low-quality study comparing cimetropium bromide with placebo showed reduced crying duration among infants treated with cimetropium bromide (MD -30.20 minutes per crisis, 95% CI -39.51 to -20.89; 86 infants). The same study reported that cimetropium increased the number of responders (RR 2.29, 95% CI 1.44 to 3.64).No serious adverse events were reported for all of the agents considered, with the exception of dicyclomine, for which two of five studies reported relevant adverse effects (longer sleep 4%, wide-eyed state 4%, drowsiness 13%).

Authors' conclusions: At the present time, evidence of the effectiveness of pain-relieving agents for the treatment of infantile colic is sparse and prone to bias. The few available studies included small sample sizes, and most had serious limitations. Benefits, when reported, were inconsistent.We found no evidence to support the use of simethicone as a pain-relieving agent for infantile colic.Available evidence shows that herbal agents, sugar, dicyclomine and cimetropium bromide cannot be recommended for infants with colic.Investigators must conduct RCTs using standardised measures that allow comparisons among pain-relieving agents and pooling of results across studies. Parents, who most often provide the intervention and assess the outcome, should always be blinded.

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Conflict of interest statement

Elena Biagioli ‐ none known. Valentina Tarasco ‐ none known. Carla Lingua ‐ none known. Lorenzo Moja ‐ none known. Francesco Savino ‐ has received fees for scientific consultancy from Nestlé Italia Milano, Italy; HiPP GmbH & Co Vertrieb KG, Germany and Danone Trading BV, Amsterdam. FS receives royalties from Springer for the book Nutrizione Parenterale in Pediatria. FS declares that the book does not cover any interventions investigated in the review and is outside the submitted work. FS received payment from Federazione Italiana Medici Pediatrici Piemonte, Torino, Italy, to attend a conference to present a clinical update. FS has received travel grants/accomodation/meeting expenses from Pharmaceutical Laboratories Cana Iraklio, Attica; Radio Televisione Italiana Roma, Italy; BioGaia AB, Stockholm, Sweden; Noos, Roma, Italy; Nestlé Italy and France. FS has received personal fees from Mead Johnson Nutrition Italy; Cana, Thessaloniki, Greece; Nutricia ‐ part of Group Danone, Dubai, Kuwait; HiPP GmbH & Co Vertrieb KG, Germany; Menarini Farmaceutica, Firenze, Italy. These organisations have had no input nor involvement in any aspect of the review process during this, or previous, systematic reviews carried out by FS. FS declares that none of these companies have a real or vested interest in the findings of the review. FS is an author of two included studies (Savino 2002 and Savino 2005). Two independent review authors (EB and VT) evaluated those studies.

Figures

1
1
Study flow diagram.
2
2
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
3
3
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
4
4
Forest plot of comparison: 1 Simethicone versus placebo, outcome: 1.2 Responders.
5
5
Forest plot of comparison: 2 Herbal agents versus placebo, outcome: 2.1 Reduction in crying duration.
6
6
Forest plot of comparison: 2 Herbal agents versus placebo, outcome: 2.2 Responders.
1.1
1.1. Analysis
Comparison 1 Simethicone versus placebo, Outcome 1 Reduction in crying duration.
1.2
1.2. Analysis
Comparison 1 Simethicone versus placebo, Outcome 2 Responders.
2.1
2.1. Analysis
Comparison 2 Herbal agents versus placebo or no intervention, Outcome 1 Reduction in crying duration.
2.2
2.2. Analysis
Comparison 2 Herbal agents versus placebo or no intervention, Outcome 2 Sensitivity: reduction in crying duration.
2.3
2.3. Analysis
Comparison 2 Herbal agents versus placebo or no intervention, Outcome 3 Responders.
3.1
3.1. Analysis
Comparison 3 Sugar versus no intervention, Outcome 1 Reduction in crying duration.
4.1
4.1. Analysis
Comparison 4 Dicyclomine versus placebo, Outcome 1 Responders.
5.1
5.1. Analysis
Comparison 5 Cimetropium bromide versus placebo, Outcome 1 Reduction in crying duration.
5.2
5.2. Analysis
Comparison 5 Cimetropium bromide versus placebo, Outcome 2 Responders.
5.3
5.3. Analysis
Comparison 5 Cimetropium bromide versus placebo, Outcome 3 Reduction in frequency of crying episodes.
6.1
6.1. Analysis
Comparison 6 Cimetropium bromide 1.2 mg/kg versus cimetropium bromide 2.0 mg/kg, Outcome 1 Reduction in frequency of crying episodes.
7.1
7.1. Analysis
Comparison 7 Simethicone versus herbal agents (Mentha piperita), Outcome 1 Reduction in crying duration.
7.2
7.2. Analysis
Comparison 7 Simethicone versus herbal agents (Mentha piperita), Outcome 2 Responders.
7.3
7.3. Analysis
Comparison 7 Simethicone versus herbal agents (Mentha piperita), Outcome 3 Reduction in frequency of crying episodes.
8.1
8.1. Analysis
Comparison 8 Sugar versus herbal agents, Outcome 1 Reduction in crying duration.
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